ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1304G>A (p.Arg435His) (rs1060501879)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000464366 SCV000547756 pathogenic Fanconi anemia 2019-02-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 435 of the FANCA protein (p.Arg435His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with Fanconi anemia (PMID: 19367192, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 408183). This variant has been reported to affect FANCA protein function (PMID: 29098742). This variant disrupts the p.Arg435 amino acid residue in FANCA. Other variant(s) that disrupt this residue have been observed in individuals with FANCA-related conditions (PMID: 12444097, 15523645, 11739169, 10090479), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Leiden Open Variation Database RCV001256354 SCV001425785 pathogenic Fanconi anemia, complementation group A 2020-02-28 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Sue Richards.

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